Divergent total synthesis of the revised structures of marine anti-cancer meroterpenoids (+)-dysiherbols A-E.
Divergent total synthesis of the revised structures of marine anti-cancer meroterpenoids (+)-dysiherbols A-E.
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DOI：
10.1039/d3sc00173c
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发表时间：
2023-03-22
期刊：
影响因子：
8.4
通讯作者：
Lu, Zhaoyong
中科院分区：
文献类型：
--
作者：
Chong, Chuanke;Chang, Le;Grimm, Isabelle;Zhang, Qunlong;Kuang, Yang;Wang, Bingjian;Kang, Jingyi;Liu, Wenhui;Baars, Julian;Guo, Yuanqiang;Schmalz, Hans-Guenther;Lu, Zhaoyong
本文报道了一种以二甲基predysiherbol 14为关键中间体的对映选择性全合成海洋抗癌化合物倍半萜氢醌类化合物（+）-dysiherbol A-E（6-10）的方法。详细阐述了两种不同的改进的合成方法，一种是从Wieland-Miescher酮衍生物21开始，其在通过分子内Heck反应建立6/6/5/6稠合四环核心结构之前被区域和非对映选择性地α-苄基化。第二种方法利用对映选择性的1，4-加成和Au催化的双环化来构建核心环系统。（+）-Dysiherbol A（6）由predysiherbol 14经直接环合得到，（+）-dysiherbol E（10）由14经烯丙基氧化、环合得到。14的环氧化得到烯丙醇45或意外重排的高烯丙醇44。通过反转羟基的构型，利用可逆的1，2-甲基位移和通过氧环化选择性地捕获中间体碳正离子之一，我们成功地完成了（+）-dysiheretin B-D（7-9）的全合成。（+）-dysiherbol A-E（6-10）的全合成是从二甲基predysiherbol 14开始以发散的方式完成的，这导致了对它们最初提出的结构的修改。以predysiherbol二甲基酯为关键中间体，采用对映选择性全合成方法，对海洋抗癌化合物倍半萜氢醌类化合物（+）-dysiherbol A-E进行了结构修正。
We report here a concise and divergent enantioselective total synthesis of the revised structures of marine anti-cancer sesquiterpene hydroquinone meroterpenoids (+)-dysiherbols A–E (6–10) using dimethyl predysiherbol 14 as a key common intermediate. Two different improved syntheses of dimethyl predysiherbol 14 were elaborated, one starting from Wieland–Miescher ketone derivative 21, which is regio- and diastereoselectively α-benzylated prior to establishing the 6/6/5/6-fused tetracyclic core structure through intramolecular Heck reaction. The second approach exploits an enantioselective 1,4-addition and a Au-catalyzed double cyclization to build-up the core ring system. (+)-Dysiherbol A (6) was prepared from dimethyl predysiherbol 14via direct cyclization, while (+)-dysiherbol E (10) was synthesized through allylic oxidation and subsequent cyclization of 14. Epoxidation of 14 afforded allylic alcohol 45 or unexpectedly rearranged homoallylic alcohol 44. By inverting the configuration of the hydroxy groups, exploiting a reversible 1,2-methyl shift and selectively trapping one of the intermediate carbenium ions through oxy-cyclization, we succeeded to complete the total synthesis of (+)-dysiherbols B–D (7–9). The total synthesis of (+)-dysiherbols A–E (6–10) was accomplished in a divergent manner starting from dimethyl predysiherbol 14, which led to the revision of their originally proposed structures. A concise and divergent enantioselective total synthesis of the revised structures of marine anti-cancer sesquiterpene hydroquinone meroterpenoids (+)-dysiherbols A–E was accomplished using dimethyl predysiherbol as a key common intermediate.
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影响因子：
2.1
作者：
AMORESE, A;ARCADI, A;ORTAR, G
通讯作者：
ORTAR, G
DOI：
10.1002/anie.201507549
发表时间：
2016-03-18
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Büschleb M;Dorich S;Hanessian S;Tao D;Schenthal KB;Overman LE
通讯作者：
Overman LE
影响因子：
2.1
作者：
Ghosh, Tapas
通讯作者：
Ghosh, Tapas
影响因子：
15
作者：
Hu, Shengkun;Tang, Yefeng
通讯作者：
Tang, Yefeng
影响因子：
5.4
作者：
Gordaliza M
通讯作者：
Gordaliza M